Critical appraisal of paroxetine for the treatment of vasomotor symptoms

Dana G Carroll, Katelin M Lisenby, Tracy L Carter, Dana G Carroll, Katelin M Lisenby, Tracy L Carter

Abstract

Background: Vasomotor symptoms (VMS), characterized by hot flashes and night sweats, are the most commonly reported symptoms associated with estrogen deficiency during menopause and occur in up to 70% of women. The goal of treatment is to reduce the frequency and severity of symptoms. Although hormone therapy (HT) is generally recommended as first-line treatment, it is not appropriate for all patients. Antidepressants, specifically selective serotonin reuptake inhibitors, have been evaluated and utilized internationally for alternative treatment for VMS. In 2013, paroxetine mesylate (Brisdelle(®)) received a US Food and Drug Administration-labeled indication for moderate-to-severe hot flashes, making it the first nonhormonal treatment for VMS associated with menopause. The objective of this review is to critically evaluate available clinical data regarding the efficacy and safety of paroxetine for the treatment of VMS in menopausal women.

Methods: MEDLINE, PubMed, and Google Scholar were searched using the keywords paroxetine, vasomotor symptoms, hot flashes, and menopause. Searches were limited to humans, English language, and clinical trial design with a primary outcome of hot flash/vasomotor changes.

Results: Paroxetine (hydrochloride and mesylate) has been associated with a 33%-67% reduction in hot flash frequency with 6-12 weeks of treatment compared to 13.7%-37.8% reductions with placebo in patients both with and without a history of breast cancer. It was also associated with significant reductions in hot flash severity. Benefits of treatment persisted through 24 weeks in the study of the longest duration. Most adverse effects reported were of mild-to-moderate severity, with improved tolerability associated with lower doses (7.5-12.5 mg/day).

Conclusion: Paroxetine is a safe and effective therapy for the treatment of VMS during menopause. Paroxetine (7.5-12.5 mg/day) should be considered a first-line therapy option for VMS in patients when HT is either inappropriate or intolerable.

Keywords: hot flashes; menopause; paroxetine; vasomotor symptoms.

References

    1. Gold EB. The timing of the age at which natural menopause occurs. Obstet Gynecol Clin North Am. 2011;38(3):425–440.
    1. American College of Obstetricians and Gynecologists Practice Bulletin No 141: management of menopausal symptoms. Obstet Gynecol. 2014;123:202–216.
    1. Goodman NF, Cobin RH, Ginzburg SB, Katz IA, Woode DE. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the diagnosis and treatment of menopause. Endocr Pract. 2011;17(suppl 6):1–25.
    1. Archer DF, Sturdee DW, Baber R, et al. Menopausal hot flushes and night sweats: where are we now. Climacteric. 2011;14(5):515–528.
    1. North American Menopause Society The 2012 hormone therapy position statement of The North American Menopause Society. Menopause. 2012;19(3):257–271.
    1. de Villiers TJ, Gass ML, Haines CJ, et al. Global consensus statement on menopausal hormone therapy. Maturitas. 2013;74(4):391–392.
    1. de Villiers TJ, Pines A, Panay N, et al. Updated 2013 International Menopause Society recommendations on menopausal hormone therapy and preventive strategies for midlife health. Climacteric. 2013;16(3):316–337.
    1. Maclennan AH, Broadbent JL, Lester S, Moore V. Oral oestrogen and combined oestrogen/progestogen therapy versus placebo for hot flushes. Cochrane Database Syst Rev. 2004;(4):CD002978.
    1. Modena MG, Sismondi P, Mueck AO, et al. Risks and benefits of estrogen plus progestin in healthy menopausal women: principle results from the Women’s Health Initiative randomized controlled trial. JAMA. 2002;288:321–333.
    1. Simon JA, Portman DJ, Kaunitz AM, et al. Low-dose paroxetine 7.5 mg for menopausal vasomotor symptoms: two randomized controlled trials. Menopause. 2013;20(10):1027–1035.
    1. Stearns V, Beebee KL, Iyengar M, Dube E. Paroxetine controlled release in the treatment of menopausal hot flashes: a randomized controlled trial. JAMA. 2003;289:2827–2834.
    1. Soares CN, Joffe H, Viguera AC, et al. Paroxetine versus placebo for women in midlife after hormone discontinuation. Am J Med. 2008;121:159–162.
    1. Stearns V, Isaacs C, Rowland J, et al. A pilot trial assessing the efficacy of paroxetine hydrocholoride (Paxil) in controlling hot flashes in breast cancer survivors. Ann Oncol. 2000;11:17–22.
    1. Weitzner MA, Moncello J, Jacobsen PB, Minton S. A pilot trial of paroxetine for the treatment of the hot flashes and associated symptoms in women with breast cancer. J Pain Symptom Manage. 2002;23(4):337–345.
    1. Stearns V, Slack R, Greep N, et al. Paroxetine is an effective treatment for hot flashes: results from a prospective randomized clinical trial. J Clin Oncol. 2005;23(28):6919–6930.
    1. U.S. Department of Health and Human Services, Food and Drug Administration, Advisory Committee for Reproductive Health Drugs Paroxetine Mesylate for Treatment of Moderate to Severe Vasomotor Symptoms Associated with Menopause. [Accessed October 24, 2014]. [updated March 4, 2013]. Available from: .
    1. Catelli M, Bhaskar S, Lippman J. Pharmacokinetic properties of once-daily oral low-dose mesylate salt of paroxetine (LDMP 7.5 mg) following single and multiple doses in healthy postmenopausal women. Clin Ther. 2013;35(6):862–869.
    1. Cubeddu A, Giannini A, Bucci F, et al. Paroxetine increased brain derived neurotrophic factor in menopausal women. Menopause. 2010;17(2):338–343.
    1. Yasui T, Yamada M, Uemura H, et al. Changes in circulating cytokine levels in midlife women with psychological symptoms with selective serotonin reuptake inhibitor and Japanese traditional medicine. Maturitas. 2009;62(2):146–152.
    1. Ushiroyama T, Ikeda A, Ueki M. Evaluation of double-blind comparison of fluvoxamine and paroxetine in the treatment of depressed outpatients in menopause transition. J Med. 2004;35(1–6):151–162.
    1. Nolvadex (tamoxifen citrate) [package insert] Wilmington, Delaware: AstraZeneca Pharmaceuticals LP; [Accessed February 6, 2015]. [updated August, 2004]. Available from: .
    1. National Comprehensive Cancer Network Breast cancer (Version 3.2014) [Accessed October 29, 2014]. [updated 2014]. Available from: .
    1. Burstein HJ, Temin S, Anderson H, et al. Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: American Society of Clinical Oncology clinical practice guideline focused update. J Clin Oncol. 2014;32(21):2255–2269.
    1. Visvanathan K, Hurley P, Bantug E. Use of pharmacologic interventions for breast cancer risk reduction: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2013;31(23):2942–2962.
    1. National Institute for Health and Care Excellence Advanced breast cancer, diagnosis and treatment. [Accessed December 29, 2014]. [updated 2014]. Available from: .
    1. National Institute for Health and Care Excellence Early and locally advanced breast cancer, diagnosis and treatment. [Accessed December 29, 2014]. [updated 2014]. Available from: .
    1. Stearns V, Johnson MD, Rae JM, et al. Active tamoxifen metabolite plasma concentrations after coadministration of tamoxifen and the selective serotonin reuptake inhibitor paroxetine. J Natl Cancer Inst. 2003;95(23):1758–1764.
    1. Jin Y, Desta Z, Stearns V, et al. CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment. J Natl Cancer Inst. 2005;97(1):30–39.
    1. Kelly CM, Juurlink DN, Gomes T, et al. Selective serotonin reuptake inhibitors and breast cancer mortality in women receiving tamoxifen: a population based cohort study. BMJ. 2010;340:c693.
    1. American Society of Clinical Oncology Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: American Society of Clinical Oncology clinical practice guideline focused update. [Accessed December 29, 2014]. Data supplement [updated 2014]. Available from: .
    1. Pinkerton JV, Joffe H, Kazenpour K, Mekonnen H, Bhaskar S, Lippman J. Low-dose paroxetine (7.5 mg) improves sleep in women with vasomotor symptoms associated with menopause. Menopause. 2015;22(1):50–58.
    1. Portman DJ, Kaunitz AM, Kazempour K, Mekonnen H, Bhaskar S, Lippman J. Effects of low-dose paroxetine 7.5 mg on weight and sexual function during treatment of vasomotor symptoms associated with menopause. Menopause. 2014;21(10):1082–1090.
    1. Joffe HV. Division Director’s Summary Review for Approval of Brisdelle (paroxetine mesylate) [Accessed March 19, 2015]. [updated June 28, 2013]. Available from: .
    1. RED BOOK [AUHSOP intranet database] Greenwood Village, CO: Truven Health Analytics; [Accessed December 14, 2014]. Paroxetine. [updated daily]. Available from: .
    1. Paxil CR. (paroxetine hydrochloride) controlled release tablets [package insert] Mississauga, ON: GlaxoSmithKline Inc; [Accessed October 24, 2014]. [updated March, 2014]. Available from: .

Source: PubMed

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